Our long-term goal is to understand alphaherpesviral pathogenesis, latency and reactivation from the perspective of the virus-natural host interaction. For this purpose, we must delineate the molecular changes that occur in the infected animal and link pattems of gene expression to biological measures of disease. Here we propose to use in vitro infections of immortalized porcine neuronal cells to study acute and potentially latent, Aujeszky's disease virus (ADV) infection. Subsequently, in vivo challenges using wild type and deletion mutant ADV genotypes will be used to study the establishment of latency and reactivation in swine by employing DNA microarrays (swine and ADV). We hypothesize that the neuron experiences differential gene expression with a concomitant change in viral gene expression from the acute to the latent ADV infection. Furthermore, changes in host cell gene expression profile is the initiating event for viral reactivation, Thus, a determination of the sequential order of natural host gene expression required for the events enabling viral latency and reactivation should provide a basic understanding of this here to for unresolved phenomenon. Elucidation of such mechanistic knowledge would benefit attempts to design therapeutic prevention or control strategies. Our specific objectives are as follows: 1. Investigate the biology of productive (lytic phase) alphaherpesvirus infection using ADV infection of cultured immortalized swine neuronal cells. 2. Investigate the molecular events of alphaherpesviral latency using ganglionic tissue and neurons from DV-infected swine. 3. Examine the molecular events of alphaherpesviral reactivation from latency using ADV-infected swine ganglia.